Synonyms: juvenile rheumatoid arthritis, juvenile idiopathic arthritis, Still's disease, juvenile arthritis

Juvenile chronic arthritis (JCA) is a group of systemic inflammatory disorders of unknown aetiology, which cause chronic joint inflammation and affect children under the age of 16 years.¹ The subset for each patient is classified according to the presentation within the first six months from the initial onset. The three major subsets are:

• Pauciarticular-onset: with 4 or fewer joints involved. This is the most common type (about 50% of cases).
• Polyarticular-onset: with more than 4 joints involved. This accounts for 20% of cases in the UK.
• Systemic-onset: with fever, rash and arthritis.

Epidemiology

• The prevalence is estimated to be 1-2 per 1,000 children.¹
• Pauciarticular and polyarticular disease occur more frequently in girls, while both sexes are affected with equal frequency in systemic-onset disease.

Risk factors

• The spondyloarthropathies are strongly associated with HLA B27.
• Sero-positive polyarticular JCA is associated with HLA DR1 and DR4.
• Early-onset pauciarticular JCA with chronic uveitis is associated with HLA DR5 and DR8.
• Early-onset pauciarticular JCA is associated with DQW1 and DPW2.
• Systemic-onset JCA is associated with HLA DR4.

Presentation

• The diagnosis is based on the presence of arthritis that persists for at least 6 weeks, with all other causes excluded. The onset can be gradual or abrupt, with morning stiffness and joint pain.
• Joint pain is variable but may be severe and there may be a marked limp.
• Fatigue and weight loss may occur and uveitis may cause photophobia.
• Systemic-onset juvenile chronic arthritis (JCA):
  • Is characterised by spiking fevers and may be accompanied by a salmon-pink rash, which affects the trunk and extremities.
  • Some children may have a generalised myalgia. Hepatosplenomegaly is often present and there may also be lymphadenopathy.
  • Arthralgia is often present but joint swelling is unusual and a definite diagnosis of systemic-onset JCA cannot be made until the development of arthritis, which may not occur for months following the onset.
  • Pleuritis, pericarditis, peritonitis and myocarditis may occur.
• Pauciarticular disease:
  • Characteristically affects the larger joints (e.g. knees, ankles, wrists). It may be associated with uveitis (especially if antinuclear antibody (ANA) positive) or sacroiliitis.
• Pauciarticular JCA usually has an asymmetrical presentation.
• Pauciarticular JCA with sacroiliitis is characterised by involvement of the hip, sacroiliac joint, heel, foot and the Achilles tendon; the spine may also be affected and may progress to ankylosing spondylitis.
• Polyarticular disease:
  • Affects both large and small joints and is usually symmetrical. Joint involvement includes the elbows, knees, ankles, hands and feet.
  • Onset is usually insidious but may be abrupt.
  • Rheumatoid factor positive subtype: rheumatoid nodules are often present.
  • Cervical spine involvement, with risk of atlantoaxial subluxation.
  • More rarely, the temporomandibular joint, spine, hips and shoulder joints are affected.

Differential diagnosis

• Infection: septic arthritis, osteomyelitis, tuberculosis, Lyme disease.
• Postinfectious, e.g. acute rheumatic fever.
• Non-inflammatory causes such as trauma, slipped epiphysis, osteochondrosis.
• Haematological, e.g. leukaemia or haemophilia with recurrent intra-articular bleeds.
• Connective tissue disorders, e.g. systemic lupus erythematosus, scleroderma, juvenile dermatomyositis.
• Malignancy including bone tumours, neuroblastoma.
• Other possibilities include ankylosing spondylitis, psoriasis, sarcoidosis, Kawasaki disease.

Investigations

• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP): always elevated in children with systemic-onset, usually elevated in polyarticular disease, but is often normal in those with pauciarticular disease.
• FBC may show anaemia (often microcytic), lymphopenia and thrombocytopenia.
• Positive antinuclear antibody (ANA) is seen in up to 25%, especially in those with pauciarticular disease:
  • Pauciarticular with chronic iridocyclitis (type I): high frequency of ANA antibodies.
  • Pauciarticular with sacroiliitis (type II): ANA antibodies are absent.
• Rheumatoid factor is rare in children with systemic juvenile chronic arthritis (JCA) and is considered as a marker for persistence of polyarticular JCA into adulthood.
• X-rays, CT scan, MRI and bone scans are often important in establishing the diagnosis and ruling out other possible diagnoses.
• Echocardiography is performed if the child has possible systemic JCA or has fevers or orthopnoea (to rule out pericarditis).
• Dual-energy X-ray absorptiometry scanning may be important in order to assess osteopenia in a child with polyarticular JCA.
• Septic arthritis may need to be excluded by arthrocentesis.

Management

• Nondrug management includes physiotherapy and occupational therapy to maintain function and prevent deformities.
• It is important to maintain activity as much as possible but also to rest swollen joints.
• Hydrotherapy is very beneficial.
• Affected children and their families may need a great deal of emotional support and also physical aids for both home and school.

Drugs

• Non-steroidal anti-inflammatory drugs (NSAIDs), e.g. ibuprofen, naproxen.
• Analgesics including paracetamol can be used for control of pain and fever.
• As with adult rheumatoid arthritis, disease-modifying anti-rheumatic drugs (DMARDs) are now used early in the disease process:²
  • All have significant potential toxicity and require careful monitoring.
  • Methotrexate is now considered by many experts to be the most effective agent.
  • Sulfasalazine is also used but is generally not used in systemic-onset disease. Gold and penicillamine are no longer used and hydroxychloroquine is now rarely used.
  • Cytokine modulators:²
    • Adalimumab, etanercept and infliximab inhibit the activity of tumour necrosis factor alpha (TNF-alpha).
    • Adalimumab and etanercept can be used for the management of active polyarticular juvenile idiopathic arthritis.
    • Infliximab has been used in refractory polyarticular juvenile idiopathic arthritis (unlicensed indication) when other treatments have failed.
    • Etanercept has been shown to be effective and well-tolerated.³ Etanercept is recommended for children aged 4 to 17 years who have active JCA in at least five joints and whose condition has not responded adequately to methotrexate or who have been unable to tolerate treatment with methotrexate.⁴
• Intravenous gamma globulin has been used in systemic juvenile chronic arthritis (JCA) with vasculitis.
• Corticosteroids:
  • These are indicated for those children with life-threatening complications and also topically for eye involvement.
  • They are extremely effective, but systemic use is a major cause of growth restriction and bone demineralisation.
  • Low-dose may be beneficial for children with severe polyarthritis who are unresponsive to other therapies.
  • Intra-articular steroid injections may also be useful for a joint which is particularly badly affected.

Surgical

Surgical intervention such as joint replacement or synovectomy may be required.

Complications

• Osteoporosis.
• Growth restriction.
• Uveitis:
  • The prevalence of uveitis in juvenile chronic arthritis (JCA) is approximately 8-30% but, in the young pauciarticular-onset group, the prevalence may be as high as 45-57%.⁵
  • The uveitis in JCA is asymptomatic and therefore screening by slit-lamp is essential for diagnosis.⁵
• Macrophage activation syndrome: a rare and often fatal complication, which may closely resemble a flare of arthritis but causes a coagulopathy with thrombocytopenia and other abnormalities of coagulation.
• Complications from medications: both NSAIDs and DMARDs have a relatively high risk of side-effects.
• Psychosocial, behavioural and educational difficulties may occur because of limitations of disability, restriction of interacting with friends and time spent away from school.
• Complications associated with each type of JCA:
  • Systemic-onset JCA: pericarditis, haemolytic anaemia, disseminated intravascular coagulation, endarteritis in the fingers and toes, resulting in very poor circulation; myocarditis, amyloidosis.
  • Pauciarticular JCA: knee flexion contractures, reduced leg length.
  • Polyarticular JCA: skeletal abnormalities - accelerated bone age, narrowed joint spaces, swan-neck and/or boutonnière deformities, and joint subluxation; cervical spine involvement.

Prognosis⁶

• It is rarely fatal and resolves in up to 80% of affected children, who regain normal function.
• The course is unpredictable in each individual child.
• Prognosis is overall favourable but depends on the subtype:
  • Pauciarticular:
    • 80% have resolved after 15 years.
    • 15% go on to develop polyarticular arthritis and severe joint involvement.
    • Eye involvement is a major problem and 50% will have reduced visual acuity at ten years after presentation and 25% will have developed cataracts or glaucoma.
    • Of the group with spondyloarthropathy, 10% are still affected after 15 years.
  • Polyarticular rheumatoid factor sero-negative: only 10-15% have severe limitation at 15 years and often go into remission with little erosive disease.
  • Polyarticular sero-positive: a more severe course with only 33% independent after 15 years.
  • Systemic-onset: 50% remit without recurrence, but the rest have polyarticular arthritis and 33% have severe destruction.
• Prognosis is worst in those with disease onset before the age of 5 years.
• About 4% die from infection or amyloidosis.

Document references

1. Rabinovich CE; Juvenile Rheumatoid Arthritis, eMedicine, Jun 2010
2. British National Formulary for Children; British Medical Association and Royal Pharmaceutical Society of Great Britain. London
3. Lovell DJ, Giannini EH, Reiff A, et al; Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000 Mar 16;342(11):763-9. [abstract]
4. Arthritis (juvenile idiopathic) - etanercept, NICE Technical Appraisal (2002); Etanercept for the treatment of juvenile idiopathic arthritis
5. Juvenile Arthritis (Guidelines for Screening for Uveitis in Juvenile Idiopathic Arthritis), Royal College of Ophthalmologists; Scroll down the list to locate.
6. Minden K, Kiessling U, Listing J, et al; Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy. J Rheumatol. 2000 Sep;27(9):2256-63. [abstract]

Acknowledgements